Quantitative genome-wide methylation analysis of high-grade non-muscle invasive bladder cancer

Kitchen, Mark O.; Bryan, Richard T.; Emes, Richard D.; Glossop, John R.; Luscombe, Christopher; Cheng, K. K.; Zeegers, Maurice P.; James, Nicholas D.; Devall, Adam J.; Mein, Charles A.; Gommersall, Lyndon; Fryer, Anthony A.; Farrell, William E.

Abstract

High-grade non-muscle invasive bladder cancer (HG-NMIBC) is a clinically unpredictable disease with greater risks of recurrence and progression relative to their low-intermediate-grade counterparts. The molecular events, including those affecting the epigenome, that characterise this disease entity in the context of tumour development, recurrence and progression, are incompletely understood. We therefore interrogated genome-wide DNA methylation using HumanMethylation450 BeadChip-arrays in 21 primary HG-NMIBC tumours relative to normal bladder controls. Using strict inclusion-exclusion criteria we identified 1,057 hypermethylated CpGs within gene promoter-associated CpG islands, representing 256 genes. Bisulphite Pyrosequencing validated the array data and examined 25 array-identified candidate genes in an independent cohort of 30 HG-NMIBC and 18 low-intermediate-grade NMIBC. These analyses revealed significantly higher methylation frequencies in high-grade tumours relative to low-intermediate-grade tumours for the ATP5G2, IRX1 and VAX2 genes (p

• Journal Article Type: Article
• Acceptance Date: Feb 8, 2016
• Online Publication Date: Mar 1, 2016
• Publication Date: Apr 6, 2016
• Deposit Date: Nov 9, 2016
• Publicly Available Date: Nov 9, 2016
• Journal: Epigenetics
• Print ISSN: 1559-2294
• Electronic ISSN: 1559-2308
• Publisher: Taylor and Francis
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 3
• Pages: 237-246
• DOI: https://doi.org/10.1080/15592294.2016.1154246
• Keywords: Epigenetics, High-grade non-muscle invasive bladder cancer, Human Methylation 450, BeadChip array, Gene expression, Methylation
• Public URL: https://nottingham-repository.worktribe.com/output/774406
• Publisher URL: http://www.tandfonline.com/doi/abs/10.1080/15592294.2016.1154246?journalCode=kepi20
• Additional Information: The Version of Record of this manuscript has been published and is available in Epigenetics 1 March 2016 http://www.tandfonline.com/10.1080/15592294.2016.1154246